Monoclonal and polyclonal antibodies are useful for a variety of purposes. The precise antigen specificity of antibodies makes them powerful tools that can be used for the detection, quantitation, purification and neutralization of antigens.
Polyclonal antibodies are produced in vivo by immunizing animals, such as rabbits and goats, with antigens, bleeding the animals and isolating polyclonal antibody molecules from the blood. Monoclonal antibodies are produced by hybridoma cells, which are made by fusing, in vitro, immortal plasmacytoma cells with antibody producing cells (Kohler, G. and C. Milstein, Nature, 256:495 (1975)) obtained from animals immunized in vivo with antigen.
Current methods for producing polyclonal and monoclonal antibodies are limited by several factors. First, methods for producing either polyclonal or monoclonal antibodies require an in vivo immunization step. This can be time consuming and require large amounts of antigen. Second, the repertoire of antibodies expressed in vivo is restricted by physiological processes, such as those which mediate self-tolerance that disable auto-reactive B cells (Goodnow, C. C., et al., Nature, 334:676 (1988); Goodnow, J. W., Basic and Clinical Immunology, Ed. 5, Los Altos, Calif., Large Medical Publications (1984); Young, C. R., Molecular Immunology, New York, Marcel Dekker (1984)). Third, although antibodies can exist in millions of different forms, each with its own unique binding site for antigen, antibody diversity is restricted by genetic mechanisms for generating antibody diversity (Honjo, T., Ann. Rev. Immunol., 1:499 (1983); Tonegawa, S., Nature: 302:575 (1983)). Fourth, not all the antibody molecules which can be generated will be generated in a given animal. As a result, raising high affinity antibodies to a given antigen can be very time consuming and can often fail. Fifth, the production of human antibodies of desired specificity is very problematical.
A method of producing antibodies which avoids the limitations of presently-available methods, such as the requirement for immunization of an animal and in vivo steps, would be very useful, particularly if it made it possible to produce a wider range of antibody types than can be made using presently-available techniques and if it made it possible to produce human antibody types.